Abdominal Aortic Aneurysms: Basic Mechanisms and Clinical Implications

doi:10.1067/msg.2002.121421

Current Problems in Surgery

Volume 39, Issue 2, February 2002, Pages 110-230

https://doi.org/10.1067/msg.2002.121421 Get rights and content

Abstract

Curr Probl Surg 2002;39:110-230.

Section snippets

Ruptured AAAs

Most AAAs do not cause symptoms until late in their natural history, when they have the potential for spontaneous rupture. Ruptured AAAs represent an immediate emergency, with an overall mortality rate greater than 90%. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnosis and the need for emergency operation in elderly individuals, who frequently have significant cardiopulmonary and renal comorbidity. Even with prompt

Structure of the normal aorta

The vertebrate aorta is responsible for efficiently transmitting pulsatile arterial blood pressure to all points in the arterial tree, a function that depends primarily on its properties as an elastic conduit. The aorta must also bear a continuous mechanical load and thereby retain its functional capacity over a lifetime of hemodynamic wall stress. The aortic wall therefore requires the properties of resilience to cyclic deformation, of resistance to structural failure, and of durability over

Pathophysiologic processes in aneurysmal degeneration

One of the important concepts that has emerged over the past 2 decades is that aneurysm disease represents a complicated and dynamic pathophysiologic process rather than a static pathologic problem; moreover, AAAs develop insidiously and expand gradually over time (Fig 1). Knowledge of the pathophysiologic processes that determine the course of aneurysmal degeneration is a crucial step toward understanding this disease in sufficient detail to develop new therapeutic strategies. The following

SMC apoptosis and senescence

Although increased proteolytic activity is now widely accepted as a major factor in the pathogenesis of AAAs, it is also becoming apparent that impaired connective tissue repair may also be critically important, either in the gradual progression of disease or in precipitating aneurysm rupture. The stability of established AAAs is likely dependent on a substantial increase in collagen production, given the enormous increase in tensile wall stress as the aorta dilates. Adventitial fibroblasts and

The interface between biomechanics and molecular biology

Given the importance of elastin and collagen in aortic wall structure and the biophysical demands placed on the aortic wall during aneurysmal dilatation, it is somewhat perplexing that AAAs should develop slowly and expand in a gradual fashion, rather than develop instantaneously with immediate rupture. It is therefore informative to ask why aneurysms do not rupture earlier in their natural history, or what factors trigger rupture in previously stable lesions. An understanding for these

Lessons learned from animal models

Studies using animal models of AAAs have provided important insights into the pathophysiologic features of AAAs, particularly in the past decade. These experimental systems have also provided essential tools to evaluate the potential for new therapeutic strategies to suppress aneurysmal degeneration in vivo. Although the present discussion is focused on models with which the authors have direct experience and greatest familiarity, interested readers will find more detail on other models in

T: Pharmacologic strategies and biomarkers

Despite the enthusiasm surrounding basic knowledge and new pathophysiologic concepts of aneurysm disease, no therapeutic approaches have proved to reduce the rate of aneurysm expansion in patients. Given that several pharmacologic strategies effectively suppress aneurysmal degeneration in animal models of AAAs, 1 of the challenges for the next several years will be to translate these findings to clinical application.

A blueprint for further investigation

The primary goal of this review has been to provide a current summary of basic and translational research on aortic aneurysm disease and to gain some insight into the therapeutic implications that this work may yield in the near future. Although a review of this type can provide valuable background information and a synopsis of current knowledge, it is intrinsically limited by the scope of what lies immediately ahead. This is particularly evident in the current atmosphere of biomedicine and

References (350)

JC Parodi et al.
Transfemoral intraluminal graft implantation for abdominal aortic aneurysms
Ann Vasc Surg
(1991)
LH Hollier et al.
Recommended indications for operative treatment of abdominal aortic aneurysms
J Vasc Surg
(1992)
JC Stanley et al.
Vascular surgery in the United States: workforce issues
J Vasc Surg
(1996)
J Tu et al.
The influence of surgical specialty training on the outcomes of elective abdominal aortic aneurysm surgery
J Vasc Surg
(2001)
E Hak et al.
Abdominal aortic aneurysm screening: an epidemiological point of view
Eur J Vasc Endovasc Surg
(1996)
M Wassef et al.
Pathogenesis of abdominal aortic aneurysms: a multidisciplinary research program supported by the National Heart, Lung, and Blood Institute
J Vasc Surg
(2001)
JM Davidson et al.
Control of elastin synthesis: molecular and cellular aspects
Z Indik et al.
Structure of the elastin gene and alternative splicing of elastin mRNA
V-M K|$$ ̈ah|$$ ̈ari et al.
Deletion analysis of the 5′-flanking region of the human elastin gene: delineation of functional promoter and regulatory cis-elements
J Biol Chem
(1990)
RP Mecham et al.
The elastin receptor shows structural and functional similarities to the 67-kDa tumor cell laminin receptor
J Biol Chem
(1989)

S Privitera et al.

The 67-kDa enzymatically inactive alternatively spliced variant of beta- galactosidase is identical to the elastin/laminin-binding protein

J Biol Chem

(1998)

A Hinek et al.

Recycling of the 67-kDa elastin binding protein in arterial myocytes is imperative for secretion of tropoelastin

Exp Cell Res

(1995)

MH Swee et al.

Developmental regulation of elastin production. Expression of tropoelastin pre-mRNA persists after down-regulation of steady-state mRNA levels

J Biol Chem

(1995)

G Peterszegi et al.

Lymphocytes in human atherosclerotic plaque exhibit the elastin-laminin receptor: potential role in atherogenesis

Atherosclerosis

(1997)

H Sakamoto et al.

Cell-type specific recognition of RGD- and non-RGD-containing cell binding domains in fibrillin-1

J Biol Chem

(1996)

RE Magenis et al.

Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1

Genomics

(1991)

HC. Dietz

Molecular etiology, pathogenesis and diagnosis of the Marfan syndrome

Prog Pediatr Cardiol

(1996)

F. Ramirez

Fibrillin mutations in Marfan syndrome and related phenotypes

Curr Opin Genet Dev

(1996)

MA Gibson et al.

The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissues

J Biol Chem

(1989)

MA Gibson et al.

Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of the elastin-associated microfibrils

J Biol Chem

(1991)

P Brown-Augsburger et al.

Microfibril-associated glycoprotein binds to the carboxyl-terminal domain of tropoelastin and is a substrate for transglutaminase

J Biol Chem

(1994)

MA Gibson et al.

Further characterization of proteins associated with elastic fiber microfibrils including the molecular cloning of MAGP-2

J Biol Chem

(1996)

G Hatzinikolas et al.

The exon structure of the human MAGP-2 gene: similarity with the MAGP-1 gene is confined to two exons encoding a cysteine-rich region

J Biol Chem

(1998)

DJ Prockop et al.

Procollagen N-proteinase and procollagen C-proteinase: two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling

Matrix Biol

(1998)

J Satta et al.

Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by measuring the concentration of the aminoterminal propeptide of type III procollagen in peripheral and aortal blood samples

J Vasc Surg

(1995)

LI Smith-Mungo et al.

Lysyl oxidase: properties, regulation and multiple functions in biology

Matrix Biol

(1998)

B Sonesson et al.

Sex difference in the mechanical properties of the abdominal aorta in human beings

J Vasc Surg

(1994)

TJ Schlatmann et al.

Histological changes in the normal aging aorta: implication for dissecting aneurysms

Am J Cardiol

(1977)

PB. Dobrin

Pathophysiology and pathogenesis of aortic aneurysms

Surg Clin North Am

(1989)

B Sonesson et al.

Infrarenal aortic diameter in the healthy person

Eur J Vasc Surg

(1994)

KW Johnston et al.

Suggested standards for reporting on arterial aneurysms

J Vasc Surg

(1991)

D Moher et al.

Epidemiology of abdominal aortic aneurysm: the effect of differing definitions

Eur J Vasc Surg

(1992)

C Dubost et al.

Resection of an aneurysm of the abdominal aorta

Arch Surg

(1952)

AB Voorhees et al.

The use of tubes constructed from Vinyon “N” cloth in bridging arterial defects

Ann Surg

(1952)

DE Szilagyi et al.

Contribution of abdominal aortic aneurysmectomy to prolongation of life

Ann Surg

(1966)

CK Zarins et al.

Operative repair for aortic aneurysms: the gold standard

J Endovasc Surg

(1997)

Lederle FA, Wilson SE, Johnson GR, et al. The Department of Veterans Affairs Aneurysm Detection and Management (ADAM)...

SR Craig et al.

Abdominal aortic aneurysm: still missing the message

Br J Surg

(1993)

J Cronenwett et al.

The Dartmouth Atlas of Vascular Health Care

(2000)

HG Alcorn et al.

Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study

Arterioscler Thromb Vasc Biol

(1996)

FA Lederle et al.

Prevalence and associations of abdominal aortic aneurysm detected through screening

Ann Int Med

(1997)

RA Scott et al.

Abdominal aortic aneurysm in 4237 screened patients: prevalence, development and management over 6 years

Br J Surg

(1991)

TR. Cheatle

The case against a national screening programme for aortic aneurysms

Ann R Coll Surg Engl

(1997)

RA Scott et al.

Influence of screening on the incidence of ruptured abdominal aortic aneurysms: 5-year results of a randomized controlled study

Br J Surg

(1995)

DE Khoo et al.

Is screening once at age 65 an effective method for detection of abdominal aortic aneurysms?

J Med Screen

(1994)

ME Emerton et al.

Screening for abdominal aortic aneurysm: a single scan is enough

Br J Surg

(1994)

H Wolinsky et al.

A lamellar unit of aortic medial structure and function in mammals

Circ Res

(1967)

H Wolinsky et al.

Comparison of abdominal and thoracic aortic medial structure in mammals: deviation of man from the usual pattern

Circ Res

(1969)

H Wolinsky et al.

Nature of species differences in the medial distribution of aortic vasa vasorum in mammals

Circ Res

(1967)

FH. Silver

Relationship between hierarchical structure and mechanical properties of the arteries

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Epicardial adipose tissue volume is associated with abdominal aortic aneurysm expansion
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The epicardial adipose tissue volume (EATV) is associated with cardiovascular diseases such as coronary artery disease. However, no information is available regarding the relationship between the EATV and abdominal aortic aneurysm (AAA) expansion. In the present study, we evaluated the association between the EATV and AAA growth and sought to identify the predictors of AAA expansion.
Between June 2009 and December 2019, 906 patients had undergone endovascular or open repair of AAAs at our institution. Patients with previous cardiac surgery, previous ascending thoracic aortic surgery, a ruptured AAA, an infected AAA, an inflammatory AAA, a saccular aneurysm, a solitary iliac aneurysm, or reintervention after treatment of the AAA were excluded. A total of 237 patients with at least two preoperative computed tomography (CT) scans performed >180 days apart were included in the present study. The EATV within the pericardium was retrospectively quantified from the preoperative non–contrast-enhanced CT images using a three-dimensional workstation. The EATV index was defined as the EATV divided by the body surface area. The AAA expansion rate was defined as an increase in the AAA diameter annually, and the patients were divided into the slow-expansion group (expansion rate, <5 mm/y) and the fast-expansion group (expansion rate, ≥5 mm/y). The correlation between the expansion rate and the EATV index was analyzed, and the cutoff value for the EATV index was determined using a receiver operating characteristics curve. Multivariate analysis was used to assess the predictors of the AAA expansion rate.
The expansion rate of AAA correlated positively with the EATV index (R = 0.237; P < .001). The initial aneurysm diameter (P < .001) and EATV index (P = .009) differed significantly between the two groups. The cutoff for the EATV index was 60.3 cm³/m² (area under the curve, 0.658; 95% confidence interval [CI], 0.568–0.749; sensitivity, 1.000; specificity, 0.309). Multivariate analysis revealed that the initial aneurysm diameter and an EATV index of >60.3 cm³/m² were significantly associated with the AAA expansion rate.
The results of the present study have demonstrated that the EATV index is associated with AAA expansion.
Clinical features of tuberculous pseudoaneurysm and risk factors for mortality
2022, Journal of Vascular Surgery
The objective of this study was to determine the clinical features of tuberculous aneurysms and risk factors for mortality.
We reviewed all case reports of tuberculous aneurysms in the English literature from January 2000 to December 2020. The clinical features and possible risk factors for mortality were recorded and analyzed.
In total, 174 cases of tuberculous aneurysms were identified. The morbidity of men was more than twice that of women. Male patients (51.47 ± 20.67 years) were older than female patients (39.52 ± 20.23 years; P < .05). The rupture rate in women (69.2%) was higher than that in men (48.8%). Tuberculosis (TB)-induced aneurysms often spontaneously ruptured 1.41 to 3.01 months after the onset of TB symptoms without any treatment, and Bacillus Calmette-Guerin (BCG)-induced aneurysms often spontaneously ruptured 10.51 to 26.49 months after BCG administration. The morbidity of large artery aneurysms was nearly twice that of middle artery aneurysms. However, middle artery aneurysms were more likely to rupture (75.4%) than large artery aneurysms (43.5%; P < .05). The rupture rate of BCG-induced aneurysms (37.0%) was lower than that of TB-induced aneurysms, regardless of whether there was a TB history (56.7%) or not (57.7%). Symptoms of TB occurred in 63.2% of patients, but only 8.6% of patients had both symptoms of TB and aneurysmal mass effects. Pain was the most common atypical clinical manifestation (50.0%). The Cox proportional hazards regression analysis and Kaplan-Meier estimator showed that rupture and no combined therapy were risk factors for mortality.
Tuberculous aneurysms seemingly shared the same demographic characteristics as common aneurysms. The clinical features of TB-induced aneurysms were different from those of BCG-induced aneurysms in terms of the aneurysm location and rupture rate. Tuberculous aneurysms may occur at any site of the cardiovascular system with a preponderance for large arteries. The changeable clinical manifestations were important index for diagnosis, but focusing only on clinical manifestations may lead to a missed diagnosis. The combination of anti-TB medications and surgery before aneurysm rupture may provide the best prognosis.
Structurally abnormal collagen fibrils in abdominal aortic aneurysm resist platelet adhesion
2022, Journal of Thrombosis and Haemostasis
Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently identified the presence of abnormal collagen fibrils with compromised D‐periodic banding in the extracellular matrix remodeling present in abdominal aortic aneurysms (AAA).
In this study, we employed multimodal microscopy approaches to characterize how collagen fibril structure impacts platelet adhesion in clinical AAA tissues.
Ultrastructural atomic force microscopy (AFM) analysis was performed on tissue sections after staining with fluorescently labeled collagen hybridizing peptide (CHP) to recognize degraded collagen. Second harmonic generation (SHG) microscopy was used on CHP‐stained sections to identify regions of intact versus degraded collagen. Finally, platelet adhesion was identified via SHG and indirect immunofluorescence on the same tissue sections.
Our results indicate that ultrastructural features characterizing collagen fibril abnormalities coincide with CHP staining. SHG signal was absent from CHP‐positive regions. Additionally, platelet binding was primarily localized to regions with SHG signal. Abnormal collagen fibrils present in AAA (in SHG negative regions) were thus found to inhibit platelet adhesion compared to normal fibrils.
Our investigations reveal how the collagen fibril structure in the vessel wall can serve as another regulator of platelet–collagen adhesion. These results can be broadly applied to understand the role of collagen fibril structure in regulating thrombosis or bleeding disorders.
Factors affecting vitamin D status in outpatients with abdominal aortic aneurysm and peripheral artery disease- a single centre study
2021, Nutrition, Metabolism and Cardiovascular Diseases
Vitamin D (VD) deficiency is considered an important risk factor for the development of atherosclerosis and aortic aneurysms. The deficiency is claimed to enhance degeneration and remodeling of collagen and elastin fibers in the artery wall, leading to its weakening and progressive dilatation.
This study aimed to assess vitamin D status, in outpatients with abdominal aneurysms (AAA) and peripheral artery disease (PAD) not treated with VD, and factors affecting serum 25-OH-D levels.
This cross-sectional study involved 59 outpatients with AAA and 150 with PAD. AAA was defined as local dilation of the aorta diameter >30 mm in imaging. None of the patients was prescribed VD containing medicines. Serum 25-OH, iPTH, phosphorus and calcium levels were assessed in all study participants. VD status was categorized according to commonly used cut-offs for serum 25-OH-D (<20 ng/mL – deficiency, <30 ng/mL –insufficiency). Serum 25-OH-D levels were similar in patient with AAA and PAD [1-3Q: 26.2 (18.8–37.6) vs 21.8 (15.9–31.4) ng/mL; p = 0.30], with deficiency noted in 25.4% with AAA and 41.8% with PAD (p < 0.05). Multiple regression analysis revealed that VD deficiency was explained by past stroke episodes [OR = 2.80 (95%CI: 1.22–6.41)]. Secondary hyperparathyroidism was diagnosed in 1.7% of patients with AAA and 1.9% with PAD.
The frequency of VD deficiency in outpatient with AAA is not greater than in those with PAD. Past stroke episode is associated with an increased occurrence of VD deficiency in both outpatients with AAA and PAD other than sun exposure and diet.
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Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease characterized by chronic inflammatory cell infiltration. We investigated the roles played by IFI16 and ASC inflammasomes in AAA development and progression.
Western blot and qRT-PCR studies were performed to analyze the expression of relative genes in AAA specimens and mouse vascular smooth muscle cells (VSMCs). The apoptosis rates and ROS levels of VSMCs were assessed by flow cytometry. Transwell assays were performed to analyze the migration ability of VSMCs. The levels of MCP-1, IL-1β, and IL-6 in the supernatants of cultured VSMCs were analyzed by ELISA.
Increased levels of IFI16 expression were found in AAA specimens and Ang-II-treated VSMCs. IFI16 and ASC silencing suppressed the apoptosis and migration ability of VSMCs undergoing Ang-II treatment, reduced elasticity damage to the aortic wall, and decreased the levels of MMP expression. The effect of IFI16 knockdown in Ang-II-induced VSMCs was reversed by MCPIP1 overexpression.
Our data suggest that an up-regulation of IFI16 and ASC expression might promote the apoptosis of VSMCs, enhance the inflammatory response, and impairs vascular wall elasticity via a MCPIP1-related mechanism. The inflammasome components IFI16 and ASC might be involved in AAA progression and serve as target molecules for diagnosing and treating AAA.
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Abdominal Aortic Aneurysms: Basic Mechanisms and Clinical Implications

Abstract

Section snippets

Ruptured AAAs

Structure of the normal aorta

Pathophysiologic processes in aneurysmal degeneration

SMC apoptosis and senescence

The interface between biomechanics and molecular biology

Lessons learned from animal models

T: Pharmacologic strategies and biomarkers

A blueprint for further investigation

Ann Vasc Surg

J Vasc Surg

J Vasc Surg

J Vasc Surg

Eur J Vasc Endovasc Surg

J Vasc Surg

J Biol Chem

J Biol Chem

J Biol Chem

Exp Cell Res

J Biol Chem

Atherosclerosis

J Biol Chem

Genomics

Prog Pediatr Cardiol

Curr Opin Genet Dev

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Matrix Biol

J Vasc Surg

Matrix Biol

J Vasc Surg

Am J Cardiol

Surg Clin North Am

Eur J Vasc Surg

J Vasc Surg

Eur J Vasc Surg

Resection of an aneurysm of the abdominal aorta

Arch Surg

The use of tubes constructed from Vinyon “N” cloth in bridging arterial defects

Ann Surg

Contribution of abdominal aortic aneurysmectomy to prolongation of life

Ann Surg

Operative repair for aortic aneurysms: the gold standard

J Endovasc Surg

Abdominal aortic aneurysm: still missing the message

Br J Surg

The Dartmouth Atlas of Vascular Health Care

Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study

Arterioscler Thromb Vasc Biol

Prevalence and associations of abdominal aortic aneurysm detected through screening

Ann Int Med

Abdominal aortic aneurysm in 4237 screened patients: prevalence, development and management over 6 years

Br J Surg

The case against a national screening programme for aortic aneurysms

Ann R Coll Surg Engl

Influence of screening on the incidence of ruptured abdominal aortic aneurysms: 5-year results of a randomized controlled study

Br J Surg

Is screening once at age 65 an effective method for detection of abdominal aortic aneurysms?

J Med Screen

Screening for abdominal aortic aneurysm: a single scan is enough

Br J Surg

A lamellar unit of aortic medial structure and function in mammals

Circ Res

Comparison of abdominal and thoracic aortic medial structure in mammals: deviation of man from the usual pattern

Circ Res

Nature of species differences in the medial distribution of aortic vasa vasorum in mammals

Circ Res

Relationship between hierarchical structure and mechanical properties of the arteries